RGS14

Summary

RGS14 (regulator of G protein signaling 14, HGNC:9996) is a protein-coding gene on chromosome 5q35.3, encoding Regulator of G-protein signaling 14 (O43566). Regulates G protein-coupled receptor signaling cascades.

This gene encodes a member of the regulator of G-protein signaling family. This protein contains one RGS domain, two Raf-like Ras-binding domains (RBDs), and one GoLoco domain. The protein attenuates the signaling activity of G-proteins by binding, through its GoLoco domain, to specific types of activated, GTP-bound G alpha subunits. Acting as a GTPase activating protein (GAP), the protein increases the rate of conversion of the GTP to GDP. This hydrolysis allows the G alpha subunits to bind G beta/gamma subunit heterodimers, forming inactive G-protein heterotrimers, thereby terminating the signal. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized.

Source: NCBI Gene 10636 — RefSeq curated summary.

At a glance

• GWAS associations: 33
• Clinical variants (ClinVar): 88 total
• MANE Select transcript: NM_006480

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9996
Approved symbol	RGS14
Name	regulator of G protein signaling 14
Location	5q35.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000169220
Ensembl biotype	protein_coding
OMIM	602513
Entrez	10636

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 9 retained_intron, 3 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000408923, ENST00000425155, ENST00000502731, ENST00000503044, ENST00000503110, ENST00000504631, ENST00000506944, ENST00000509289, ENST00000511890, ENST00000512000, ENST00000512490, ENST00000514102, ENST00000514713, ENST00000896663

RefSeq mRNA: 3 — MANE Select: NM_006480 NM_001366617, NM_001366618, NM_006480

CCDS: CCDS43405

Canonical transcript exons

ENST00000408923 — 15 exons

Exon	Start	End
ENSE00001568772	177370591	177370664
ENSE00001578181	177365963	177365984
ENSE00001580683	177366177	177366355
ENSE00001583416	177366708	177366800
ENSE00002055476	177357924	177358069
ENSE00002074660	177371873	177372596
ENSE00003459174	177368717	177368920
ENSE00003475853	177366891	177367034
ENSE00003486555	177368157	177368266
ENSE00003541384	177371165	177371246
ENSE00003595693	177367714	177367825
ENSE00003614001	177367414	177367557
ENSE00003623964	177370905	177371031
ENSE00003666587	177371475	177371589
ENSE00003677132	177371350	177371396

Expression profiles

Bgee: expression breadth ubiquitous, 236 present calls, max score 98.22.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.9911 / max 294.9576, expressed in 1117 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
60472	8.4889	731
60474	0.4712	274
60475	0.4442	203
60473	0.3677	160
60471	0.1666	39
60476	0.0353	17
60470	0.0171	6

Top tissues by expression

277 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	98.22	gold quality
caudate nucleus	UBERON:0001873	97.60	gold quality
putamen	UBERON:0001874	97.59	gold quality
nucleus accumbens	UBERON:0001882	97.08	gold quality
right lobe of liver	UBERON:0001114	96.11	gold quality
lower esophagus mucosa	UBERON:0035834	95.67	gold quality
blood	UBERON:0000178	95.38	gold quality
monocyte	CL:0000576	94.65	gold quality
spleen	UBERON:0002106	94.41	gold quality
leukocyte	CL:0000738	94.37	gold quality
mononuclear cell	CL:0000842	94.19	gold quality
esophagus mucosa	UBERON:0002469	93.17	gold quality
right uterine tube	UBERON:0001302	91.79	gold quality
lymph node	UBERON:0000029	91.28	gold quality
gall bladder	UBERON:0002110	90.33	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.86	gold quality
skin of abdomen	UBERON:0001416	89.55	gold quality
prefrontal cortex	UBERON:0000451	88.69	gold quality
metanephros cortex	UBERON:0010533	88.47	gold quality
vermiform appendix	UBERON:0001154	88.19	gold quality
bone marrow cell	CL:0002092	88.07	gold quality
amygdala	UBERON:0001876	87.98	gold quality
small intestine Peyer’s patch	UBERON:0003454	87.96	gold quality
esophagus	UBERON:0001043	87.94	gold quality
right lobe of thyroid gland	UBERON:0001119	87.93	gold quality
skin of leg	UBERON:0001511	87.69	gold quality
right frontal lobe	UBERON:0002810	87.61	gold quality
cingulate cortex	UBERON:0003027	87.14	gold quality
body of pancreas	UBERON:0001150	86.95	gold quality
anterior cingulate cortex	UBERON:0009835	86.94	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.40

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYCN

miRNA regulators (miRDB)

25 targeting RGS14, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-487A-3P	99.50	69.95	840
HSA-MIR-154-3P	99.50	70.05	831
HSA-MIR-516A-3P	99.46	67.96	1378
HSA-MIR-516B-3P	99.46	67.96	1378
HSA-MIR-4641	99.28	66.64	744
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-4763-5P	98.75	63.89	854
HSA-MIR-210-5P	98.57	64.37	832
HSA-MIR-299-3P	97.73	66.67	773
HSA-MIR-4253	97.48	65.11	692
HSA-MIR-6862-5P	97.48	64.84	713
HSA-MIR-5699-5P	97.36	67.03	1014
HSA-MIR-1913	97.07	66.20	1417
HSA-MIR-3690	96.44	65.18	737
HSA-MIR-4749-3P	96.40	66.24	798
HSA-MIR-6742-5P	96.32	64.01	869
HSA-MIR-6834-5P	96.25	64.88	823

Literature-anchored findings (GeneRIF, showing 16)

• We show that RGS14 is a component of mitotic asters formed in vitro from HeLa cell extracts and that depletion of RGS14 from cell extracts blocks aster formation. (PMID:15917656)
• NMR 1H, 13C and 15N resonances of the RGS domain (residues 56-207) (PMID:19636837)
• RGS14 serves as a novel scaffold to integrate GTP-Binding Protein alpha Subunit and Ras/Raf/MAPkinase signalling events through the action of its GL domain. (PMID:19878719)
• RGS-14 may facilitate cognitive processing by modulating Cav1 channel-mediated intracellular divalent calcium ion Ca(2)+ transients. (PMID:20842066)
• RGS14 can form complexes with GPCRs in cells that are dependent on Galpha(i/o) and these RGS14.Galpha(i1).GPCR complexes may be substrates for other signaling partners such as Ric-8A (PMID:21880739)
• The RBD region associates with the RGS domain region, producing an intramolecular interaction within RGS14 that enhances the GTPase activating function. (PMID:23255434)
• Data support the notion that the Galpha, but not Gbetagamma, arm of the Gi/o signalling is involved in TRPC4 activation and unveil new roles for RGS and RGS14 in fine-tuning TRPC4 activities. (PMID:26987813)
• The findings of this study suggested new pre- and postsynaptic regulatory functions of RGS14 and RGS14 variants, specific to the primate brain, and provide evidence for unconventional roles of RGS14 in the nuclei of striatal neuron. (PMID:28776200)
• We discovered 154 SNPs from five independent regions associated with FGF23 concentration. A locus strongly associated with variations in FGF23 concentration is rs11741640, within RGS14 and upstream of SLC34A1 (a gene involved in renal phosphate transport). (PMID:30217807)
• The rs1256328 (ALPL) and rs12654812 (RGS14) Polymorphisms are Associated with Susceptibility to Calcium Nephrolithiasis in a Taiwanese population. (PMID:31754202)
• Genetic Polymorphisms of RGS14 and Renal Stone Disease. (PMID:33309307)
• Human genetic variants disrupt RGS14 nuclear shuttling and regulation of LTP in hippocampal neurons. (PMID:33410399)
• RGS14 regulates PTH- and FGF23-sensitive NPT2A-mediated renal phosphate uptake via binding to the NHERF1 scaffolding protein. (PMID:35307350)
• RGS14 expression in CA2 hippocampus, amygdala, and basal ganglia: Implications for human brain physiology and disease. (PMID:36541898)
• Hepatic regulator of G protein signaling 14 ameliorates NAFLD through activating cAMP-AMPK signaling by targeting Gialpha1/3. (PMID:38237897)
• Distinct and overlapping RGS14 and RGS12 actions regulate NPT2A-mediated phosphate transport. (PMID:39293332)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rgs14	ENSMUSG00000052087
rattus_norvegicus	Rgs14	ENSRNOG00000015616

Paralogs (23): RGS11 (ENSG00000076344), RGS1 (ENSG00000090104), RGS17 (ENSG00000091844), AXIN1 (ENSG00000103126), RGS9 (ENSG00000108370), RGS2 (ENSG00000116741), RGS4 (ENSG00000117152), RGSL1 (ENSG00000121446), RGS13 (ENSG00000127074), RGS22 (ENSG00000132554), RGS8 (ENSG00000135824), RGS3 (ENSG00000138835), RGS5 (ENSG00000143248), RGS16 (ENSG00000143333), RGS20 (ENSG00000147509), RGS10 (ENSG00000148908), RGS18 (ENSG00000150681), RGS12 (ENSG00000159788), AXIN2 (ENSG00000168646), RGS19 (ENSG00000171700), RGS6 (ENSG00000182732), RGS7 (ENSG00000182901), RGS21 (ENSG00000253148)

Protein

Protein identifiers

Regulator of G-protein signaling 14 — O43566 (reviewed: O43566)

All UniProt accessions (2): O43566, H0Y8W3

UniProt curated annotations — full annotation on UniProt →

Function. Regulates G protein-coupled receptor signaling cascades. Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form. Besides, modulates signal transduction via G protein alpha subunits by functioning as a GDP-dissociation inhibitor (GDI). Has GDI activity on G(i) alpha subunits GNAI1 and GNAI3, but not on GNAI2 and G(o)-alpha subunit GNAO1. Has GAP activity on GNAI0, GNAI2 and GNAI3. May act as a scaffold integrating G protein and Ras/Raf MAPkinase signaling pathways. Inhibits platelet-derived growth factor (PDGF)-stimulated ERK1/ERK2 phosphorylation; a process depending on its interaction with HRAS and that is reversed by G(i) alpha subunit GNAI1. Acts as a positive modulator of microtubule polymerisation and spindle organization through a G(i)-alpha-dependent mechanism. Plays a role in cell division. Required for the nerve growth factor (NGF)-mediated neurite outgrowth. Involved in stress resistance. May be involved in visual memory processing capacity and hippocampal-based learning and memory.

Subunit / interactions. Interacts with GNAO1, GNAI2 and GNAI3. Interacts with GNAI1. Interacts (via RGS and GoLoco domains) with GNAI1; the interaction occurs in the centrosomes. Interaction with GNAI1 or GNAI3 (via active GTP- or inactive GDP-bound forms) prevents association of RGS14 with centrosomes or nuclear localization. Interacts with RABGEF1; the interactions is GTP-dependent. Interacts with RAP2A; the interactions is GTP-dependent and does not alter its function on G(i) alpha subunits either as GAP or as GDI. Associates with microtubules. Found in a complex with at least BRAF, HRAS, MAP2K1, MAPK3 and RGS14. Interacts with RIC8A (via C-terminus). Interacts (via RBD 1 domain) with HRAS (active GTP-bound form preferentially). Interacts (via RBD domains) with BRAF (via N-terminus); the interaction mediates the formation of a ternary complex with RAF1. Interacts (via RBD domains) with RAF1 (via N-terminus); the interaction mediates the formation of a ternary complex with BRAF. Interacts with KRAS (active GTP-bound form preferentially), MRAS (active GTP-bound form preferentially), NRAS (active GTP-bound form preferentially) and RRAS (active GTP-bound form preferentially).

Subcellular location. Nucleus. PML body. Cytoplasm. Membrane. Cell membrane. Cytoskeleton. Microtubule organizing center. Centrosome. Spindle. Spindle pole. Cell projection. Dendrite. Dendritic spine. Postsynaptic density.

Post-translational modifications. Phosphorylated by PKC. Phosphorylation is increased in presence of forskolin and may enhance the GDI activity on G(i) alpha subunit GNAI1.

Domain organisation. The RGS domain is necessary for GTPase-activating protein (GAP) activity for G subunits and localization to the nucleus and centrosomes. The GoLoco domain is necessary for GDP-dissociation inhibitor (GDI) activity, translocation out of the nucleus and interaction with G(i) alpha subunits GNAI1, GNAI2 and GNAI3. The RBD domains are necessary for localization to the nucleus and centrosomes.

Isoforms (4)

UniProt ID	Names	Canonical?
O43566-7	1	yes
O43566-4	2
O43566-5	3
O43566-6	4

RefSeq proteins (3): NP_001353546, NP_001353547, NP_006471* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003109	GoLoco_motif	Conserved_site
IPR003116	RBD_dom	Domain
IPR016137	RGS	Domain
IPR024066	RGS_subdom1/3	Homologous_superfamily
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR036305	RGS_sf	Homologous_superfamily
IPR037881	RGS14_RGS	Domain
IPR044926	RGS_subdomain_2	Homologous_superfamily
IPR046992	RBD1_RGS14	Domain
IPR046993	RBD2_RGS14	Domain
IPR046995	RGS10/12/14-like	Family

Pfam: PF00615, PF02188, PF02196

UniProt features (43 total): helix 11, modified residue 7, splice variant 5, region of interest 5, domain 4, compositionally biased region 3, sequence conflict 3, strand 2, turn 2, chain 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
2OM2	X-RAY DIFFRACTION	2.2
3ONW	X-RAY DIFFRACTION	2.38
3QI2	X-RAY DIFFRACTION	2.8
2XNS	X-RAY DIFFRACTION	3.41
2JNU	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43566-F1	68.58	0.31

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (7): 20, 42, 45, 199, 203, 218, 288

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-418594	G alpha (i) signalling events

MSigDB gene sets: 310 (showing top): GOBP_PLATELET_DERIVED_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, GOBP_MEMORY, RNGTGGGC_UNKNOWN, GOBP_NEGATIVE_REGULATION_OF_MAP_KINASE_ACTIVITY, GOBP_NEGATIVE_REGULATION_OF_ERK1_AND_ERK2_CASCADE, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_NEGATIVE_REGULATION_OF_KINASE_ACTIVITY, GOBP_ASSOCIATIVE_LEARNING, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, MORI_IMMATURE_B_LYMPHOCYTE_UP, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOBP_NEUROGENESIS, RACCACAR_AML_Q6

GO Biological Process (22): mitotic cell cycle (GO:0000278), nucleocytoplasmic transport (GO:0006913), response to oxidative stress (GO:0006979), spindle organization (GO:0007051), chromosome segregation (GO:0007059), G protein-coupled receptor signaling pathway (GO:0007186), learning (GO:0007612), long-term memory (GO:0007616), regulation of G protein-coupled receptor signaling pathway (GO:0008277), visual learning (GO:0008542), zygote asymmetric cell division (GO:0010070), negative regulation of synaptic plasticity (GO:0031914), negative regulation of MAP kinase activity (GO:0043407), negative regulation of G protein-coupled receptor signaling pathway (GO:0045744), platelet-derived growth factor receptor signaling pathway (GO:0048008), positive regulation of neurogenesis (GO:0050769), cell division (GO:0051301), long-term synaptic potentiation (GO:0060291), negative regulation of ERK1 and ERK2 cascade (GO:0070373), signal transduction (GO:0007165), negative regulation of signal transduction (GO:0009968), modulation of chemical synaptic transmission (GO:0050804)

GO Molecular Function (10): G-protein alpha-subunit binding (GO:0001965), GTPase activity (GO:0003924), GDP-dissociation inhibitor activity (GO:0005092), GTPase activator activity (GO:0005096), microtubule binding (GO:0008017), protein kinase binding (GO:0019901), signaling receptor complex adaptor activity (GO:0030159), GTPase activating protein binding (GO:0032794), protein binding (GO:0005515), GTPase regulator activity (GO:0030695)

GO Cellular Component (17): spindle pole (GO:0000922), nucleus (GO:0005634), cytoplasm (GO:0005737), centrosome (GO:0005813), spindle (GO:0005819), microtubule (GO:0005874), plasma membrane (GO:0005886), postsynaptic density (GO:0014069), nuclear body (GO:0016604), PML body (GO:0016605), dendrite (GO:0030425), dendritic spine (GO:0043197), glutamatergic synapse (GO:0098978), cytoskeleton (GO:0005856), membrane (GO:0016020), cell projection (GO:0042995), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
intracellular membraneless organelle	3
cell cycle process	2
G protein-coupled receptor signaling pathway	2
regulation of synaptic plasticity	2
negative regulation of MAPK cascade	2
cellular process	2
protein binding	2
GTPase regulator activity	2
GTPase activity	2
microtubule cytoskeleton	2
cell cycle	1
mitotic nuclear division	1
nuclear transport	1
response to stress	1
microtubule cytoskeleton organization	1
G protein-coupled receptor activity	1
signal transduction	1
learning or memory	1
memory	1
regulation of signal transduction	1
visual behavior	1
associative learning	1
asymmetric cell division	1
MAP kinase activity	1
regulation of MAP kinase activity	1
negative regulation of protein serine/threonine kinase activity	1
regulation of G protein-coupled receptor signaling pathway	1
negative regulation of signal transduction	1
cell surface receptor protein tyrosine kinase signaling pathway	1
positive regulation of cell development	1
neurogenesis	1
regulation of neurogenesis	1
positive regulation of nervous system development	1
positive regulation of synaptic transmission	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
cell communication	1
signaling	1
regulation of cellular process	1

Protein interactions and networks

STRING

1212 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RGS14	LRPAP1	P30533	818
RGS14	GNAO1	P09471	734
RGS14	RHPN1	Q8TCX5	716
RGS14	RAP2A	P10114	694
RGS14	SUCLG2	Q96I99	676
RGS14	PCP4	P48539	633
RGS14	HRAS	P01112	562
RGS14	AMIGO2	Q86SJ2	546
RGS14	RIC8A	Q9NPQ8	546
RGS14	RAP1A	P10113	528
RGS14	DLG4	P78352	526
RGS14	PCP2	Q8IVA1	504
RGS14	GPR35	Q9HC97	494
RGS14	TJP1	Q07157	475
RGS14	GPSM1	Q86YR5	474

IntAct

22 interactions, top by confidence:

A	B	Type	Score
RGS14	GNAI3	psi-mi:“MI:0915”(physical association)	0.800
GNAI3	RGS12	psi-mi:“MI:0914”(association)	0.640
RGS14	GNAI1	psi-mi:“MI:0915”(physical association)	0.620
GNAI1	GNAT3	psi-mi:“MI:0914”(association)	0.530
RGS14	TINF2	psi-mi:“MI:0915”(physical association)	0.510
Gnao1	RGS14	psi-mi:“MI:0407”(direct interaction)	0.440
HRAS	RGS14	psi-mi:“MI:0407”(direct interaction)	0.440
GNAI1	RGS14	psi-mi:“MI:0407”(direct interaction)	0.440
RGS14	POT1	psi-mi:“MI:0915”(physical association)	0.370
RGS14	VIPR2	psi-mi:“MI:0915”(physical association)	0.370
RGS14	NFKB1	psi-mi:“MI:0915”(physical association)	0.370
RGS14	WAS	psi-mi:“MI:0915”(physical association)	0.370
XPO1	RGS14	psi-mi:“MI:0915”(physical association)	0.370
TRAF2	RGS14	psi-mi:“MI:0915”(physical association)	0.370
CUL4B	GGTLC3	psi-mi:“MI:0914”(association)	0.350
RGS14	TINF2	psi-mi:“MI:0915”(physical association)	0.000
GNAI3	RGS14	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (37): RGS14 (Affinity Capture-MS), RGS14 (Affinity Capture-MS), RGS14 (Two-hybrid), RGS14 (Affinity Capture-MS), RGS14 (Affinity Capture-MS), RGS14 (Affinity Capture-MS), RGS14 (Two-hybrid), RGS14 (Two-hybrid), RAP2A (Reconstituted Complex), RAP1A (Reconstituted Complex), RGS14 (Reconstituted Complex), RGS14 (Reconstituted Complex), RGS14 (Affinity Capture-MS), RGS14 (Affinity Capture-MS), RGS14 (Affinity Capture-MS)

ESM2 similar proteins: A1A4I4, A1A5B6, A4D2P6, B2DCZ9, B4F7F3, O00192, O08773, O08874, O08908, O35465, O43566, O62683, O75808, O95049, P70268, P97492, Q0QWG9, Q12851, Q14164, Q14318, Q16512, Q16513, Q3B7U9, Q3KR56, Q3MII6, Q3UFB7, Q5FVC2, Q60875, Q61161, Q63433, Q63788, Q6P5Z2, Q6PFQ7, Q6V7V2, Q6ZT62, Q7Z5H3, Q865S3, Q8BWW9, Q8IYK8, Q8K045

Diamond homologs: A1A643, F1S668, O08773, O08774, O08849, O08850, O08899, O14921, O14924, O15169, O15492, O15539, O35625, O42400, O43566, O43665, O46469, O46470, O46471, O54828, O54829, O70239, O70240, O70521, O75916, O76081, O88566, O94810, P34295, P41220, P49758, P49795, P49796, P49797, P49798, P49799, P49800, P49802, P49803, P49804

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PRKACA	“up-regulates activity”	RGS14	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

88 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	66
Likely benign	5
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2466 predictions. Top by Δscore:

Variant	Effect	Δscore
5:177358066:CATGG:C	donor_loss	1.0000
5:177358067:ATGG:A	donor_loss	1.0000
5:177358068:TGG:T	donor_loss	1.0000
5:177358069:GGT:G	donor_loss	1.0000
5:177358070:GTGA:G	donor_loss	1.0000
5:177358071:T:A	donor_loss	1.0000
5:177366172:TGCAG:T	acceptor_gain	1.0000
5:177366173:GCAG:G	acceptor_loss	1.0000
5:177366174:CA:C	acceptor_loss	1.0000
5:177366174:CAG:C	acceptor_gain	1.0000
5:177366175:A:AC	acceptor_loss	1.0000
5:177366175:A:AG	acceptor_gain	1.0000
5:177366175:AGA:A	acceptor_gain	1.0000
5:177366176:G:GA	acceptor_gain	1.0000
5:177366176:GA:G	acceptor_gain	1.0000
5:177366176:GAG:G	acceptor_gain	1.0000
5:177366176:GAGC:G	acceptor_gain	1.0000
5:177366176:GAGCT:G	acceptor_gain	1.0000
5:177366353:ACT:A	donor_gain	1.0000
5:177366356:G:GG	donor_gain	1.0000
5:177366706:A:AG	acceptor_gain	1.0000
5:177366706:AG:A	acceptor_gain	1.0000
5:177366707:G:A	acceptor_loss	1.0000
5:177366707:G:GA	acceptor_gain	1.0000
5:177366707:GG:G	acceptor_gain	1.0000
5:177366707:GGA:G	acceptor_gain	1.0000
5:177366707:GGAGT:G	acceptor_gain	1.0000
5:177366796:AGCAG:A	donor_loss	1.0000
5:177366797:GCAG:G	donor_gain	1.0000
5:177366798:CAGG:C	donor_loss	1.0000

AlphaMissense

3631 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:177366711:T:C	F84L	1.000
5:177366713:C:A	F84L	1.000
5:177366713:C:G	F84L	1.000
5:177366715:T:C	L85P	1.000
5:177366729:A:C	S90R	1.000
5:177366731:C:A	S90R	1.000
5:177366731:C:G	S90R	1.000
5:177366740:C:A	N93K	1.000
5:177366740:C:G	N93K	1.000
5:177367424:T:C	L165S	1.000
5:177367436:A:C	D169A	1.000
5:177367436:A:G	D169G	1.000
5:177367436:A:T	D169V	1.000
5:177367438:A:C	S170R	1.000
5:177367440:C:A	S170R	1.000
5:177367440:C:G	S170R	1.000
5:177367451:T:C	F174S	1.000
5:177366299:T:A	W64R	0.999
5:177366299:T:C	W64R	0.999
5:177366351:T:C	F81S	0.999
5:177366712:T:C	F84S	0.999
5:177366723:G:A	E88K	0.999
5:177366726:T:C	F89L	0.999
5:177366728:C:A	F89L	0.999
5:177366728:C:G	F89L	0.999
5:177366730:G:A	S90N	0.999
5:177366736:A:T	E92V	0.999
5:177366738:A:C	N93H	0.999
5:177366738:A:G	N93D	0.999
5:177366739:A:G	N93S	0.999

dbSNP variants (sampled 300 via entrez): RS1000037908 (5:177369042 C>A,T), RS1000093969 (5:177362342 GCCAGGGT>G), RS1000277260 (5:177356160 A>G), RS1000467003 (5:177363098 G>A,C), RS1000557524 (5:177369300 C>G,T), RS1000800265 (5:177364495 C>T), RS1001100949 (5:177360710 G>A,T), RS1001163040 (5:177361410 T>A,C), RS1001472011 (5:177361322 A>G), RS1001824396 (5:177372436 C>T), RS1002051135 (5:177366015 G>A), RS1002168469 (5:177359734 C>T), RS1002222473 (5:177359427 C>G), RS1002228361 (5:177367688 T>C,G), RS1002519326 (5:177370776 A>G,T)

Disease associations

OMIM: gene MIM:602513 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

33 associations (top):

Study	Trait	p-value
GCST000649_23	Chronic kidney disease	1.000000e-14
GCST001198_73	Multiple sclerosis	5.000000e-07
GCST001432_1	Nephrolithiasis	9.000000e-12
GCST001574_7	Activated partial thromboplastin time	6.000000e-88
GCST001606_6	Renal function-related traits (sCR)	5.000000e-07
GCST001607_4	Renal function-related traits (eGRFcrea)	2.000000e-07
GCST002201_8	Calcium levels	5.000000e-06
GCST003879_3	Serum parathyroid hormone levels	3.000000e-23
GCST004131_57	Inflammatory bowel disease	4.000000e-09
GCST004133_67	Ulcerative colitis	4.000000e-08
GCST004601_66	Red blood cell count	9.000000e-10
GCST004604_100	Hematocrit	9.000000e-11
GCST004615_25	Hemoglobin concentration	1.000000e-09
GCST005038_64	Allergic disease (asthma, hay fever or eczema)	1.000000e-08
GCST005531_41	Multiple sclerosis	4.000000e-18
GCST005956_15	Waist-to-hip ratio adjusted for BMI	1.000000e-07
GCST005957_13	Waist-to-hip ratio adjusted for BMI (age <50)	3.000000e-07
GCST005962_42	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	1.000000e-08
GCST005981_2	Phosphorus levels	2.000000e-23
GCST005984_29	Glomerular filtration rate	3.000000e-16
GCST006491_8	Circulating fibroblast growth factor 23 levels	2.000000e-16
GCST007344_54	Estimated glomerular filtration rate	1.000000e-32
GCST007833_4	Urolithiasis	2.000000e-19
GCST008062_56	Blood urea nitrogen levels	1.000000e-19
GCST008064_2	Chronic kidney disease	2.000000e-10
GCST009597_301	Multiple sclerosis	3.000000e-21
GCST010083_272	Hemoglobin levels	7.000000e-16
GCST011816_4	Vitamin C levels	4.000000e-09
GCST90002381_406	Eosinophil count	1.000000e-16
GCST90002382_138	Eosinophil percentage of white cells	1.000000e-11

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0004838	calcium measurement
EFO:0004305	erythrocyte count
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0004861	phosphorus measurement
EFO:0600003	vitamin C measurement
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — R12 family

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
Z55627844	Inhibition	5.44	pIC50

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression	3
(+)-JQ1 compound	decreases expression	2
Air Pollutants	decreases expression, affects expression, increases abundance	2
Benzo(a)pyrene	affects methylation, decreases expression	2
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, affects response to substance, increases expression, affects cotreatment	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Zoledronic Acid	increases expression	1
Atrazine	increases expression	1
Caffeine	decreases phosphorylation	1
Cisplatin	affects cotreatment, increases expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression, affects cotreatment	1
Methyl Methanesulfonate	decreases expression	1
Niclosamide	increases expression	1
Ozone	affects expression, increases abundance	1
Phthalic Acids	affects methylation	1
Smoke	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	affects expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.